The broad objective of this proposal is to investigate the alterations of fasting fuel metabolism and nutrient assimulation in animal models of small for gestational age (SGA) and infants of diabetic mothers (IDM). The investigation of the relationship between neonatal intrahepatic regulaton of systemic glucose production and subsequent provision to, and utilization by the central nervous system is a more specific goal. In addition to the investigation of glucose production, specific attention will be given to the mobilization and provision of alternate substrates and gluconeogenic precursors. Glucose-amino acid and glucose-fat interrelationships will be examined in the fasted and alimented states in both pregnant dogs and her newborn pups. Systemic glucose turnover, gluconeogenesis ureagenesis, free fatty acid production and amino acid turnover will be examined with multiple radioisotopic and stable isotopic tracers. These in-vivo determinations of substrate availability will be quantified by beta scintillation and mass spectrometry. Intrahepatic regulation will be examined by determining substrate concentrations involved in key regulatory enzymatic steps of glycolysis and the Krebs cycle. In addition, the specific activity of these rate controlling enzymes will also be determined. As the potential exists in these experimental models for inducing spontaneous fasting neonatal hypoglycemia, the effects of this perturbation on cerebral energy metabolism will also be examined. In addition, the mobilization and oxidation of alternate fuel during these periods of hypoglycemia will also be investigated. Thus, models of fetal nutritional deficit (SGA) or surfeit (IDM) provide means to investigate the pattern of fuel mobilization and utilization during neontal hypoglycemia in particular, but also as an analogy to the metabolic pertubations which occur in human IDM or SGA infants.